Methylphenidate does not improve interference control during a working memory task in young patients with attention-deficit hyperactivity disorder.

Patients with attention-deficit/hyperactivity disorder (ADHD) show deficits in working memory (WM) which may be related to prefrontal dysfunction. Methylphenidate (MPH) can restore WM deficits in ADHD by enhancing prefrontal activity. At the same time, changes in striatal activation could cause ADHD patients to be more interference-sensitive during working memory tasks. However, it is unclear whether MPH reduces WM distractibility in ADHD. In this fMRI study, 12 ADHD patients and 12 healthy controls participated on two separate days in a delayed-match-to-sample test. During the delay interval, a distractor stimulus was presented in half of the trials. Children and adolescents with ADHD received MPH only on one of the two sessions. Behavioral data analyses revealed that MPH normalized WM in ADHD. However, MPH did not improve WM performance when a distractor was presented during the delay interval. Functional images showed that MPH enhanced prefrontal activity during the delay in ADHD patients when no distractor was present. If the delay was interrupted by a distractor, only healthy controls showed activation of the caudate. In patients with ADHD, however, in line with behavioral data, MPH did not enhance caudate activity. In healthy youth, caudate activity is involved in interference control allowing the successful maintenance of information in working memory even in the presence of distraction. Our findings suggest that interference control, linked to caudate activity, is not adequately enhanced by MPH in ADHD.

Hippocampus-dependent and -independent theta-networks of active maintenance.

Recent studies in humans and animals raise the possibility that actively maintaining a detailed memory of a scene within working memory may require the hippocampus, a brain structure better known for its role in long-term memory. We show that the hippocampus is behaviorally and functionally critical for configural-relational (CR) maintenance by orchestrating the synchrony of occipital and temporal brain regions in the theta-frequency range. Using magnetoencephalography in healthy adults and patients with bilateral hippocampal sclerosis, we distinguish this hippocampus-dependent theta-network from one that is independent of the hippocampus and used for non-CR scene maintenance. This non-CR theta-network involved frontal and parietal brain regions. We also show that the functional and topographical dissociation between these two networks cannot be accounted for by perceptual difficulty or the amount of information to be maintained ("load"). Also, we confirm in healthy adults that active maintenance of the CR arrangement of objects within a scene is impaired by task-interference during the delay in a manner akin to working-memory maintenance processes. Together, these findings demand reconsideration of the classical functional-anatomical distinctions between long- and short-term memory.

Neural generators of sustained activity differ for stimulus-encoding and delay maintenance.

The ability to maintain information online beyond sensory stimulation is regarded as a key contribution of working memory to goal-directed behaviour. It is widely accepted that sustained neural activity is a key mechanism of stimulus maintenance, but it is unclear to what extent the neural generators of sustained activity change from stimulus-encoding to maintenance. Using event-related potentials in humans, we show that, in a delayed match-to-sample task, slow shifts over parieto-occipital electrode sites had a different topography and polarity during encoding and delay maintenance of images depicting scenes. This clearly demonstrates that neural generators of sustained activity associated with stimulus-encoding and delay maintenance differed, and that the change between these generators occurred time-locked to the onset of the delay period. We also investigated how monetary reward incentives modulated the amplitude and topography of sustained delay activity and the ability to suppress irrelevant distracting information during the delay. Reward incentives improved maintenance performance and this was correlated with an expansion of the parieto-occipital electrode sites that were entrained into sustained delay activity (rather than improved distractor suppression), suggesting that under the influence of reward, the parieto-occipital regions that contributed to delay maintenance expanded in size.